Adrenergic and noradrenergic plasma levels in Lesch-Nyhan disease

Noradrenergic dysfunction and abnormality in monoamine oxidase (MAO) enzyme activity have been reported previously in Lesch-Nyhan (LN) disease. This s tudy examines peripheral indices of adrenergic, noradrenergic, and MAO func tion in children and young adults with LN disease (n = 11), and healthy sub jects (n = 9). Blood samples, collected in identical conditions prior to a positron emission tomography (PET) study, were assayed for concentrations o f epinephrine (EPI), norepinephrine (NE), and 3-methoxy-4-hydroxyphenylglyc ol (DHPG) (which results from the degradation of NE by monoamine oxidase ty pe A [MAO-A]). The LN subjects had significantly higher EPI levels by 245% (p < .00) and lower DHPG levels by 42% (p <.00) compared to the control gro up. No group differences were noted in NE plasma levels. Cognitive function (IQ tested by Stanford Binet intelligence Scale) was associated with EPI i n the LN group (r = 0.77, p = .009), but not in the control group. The abno rmally high EPI plasma concentrations may indicate another biochemical dysf unction secondary to the absence of the HPRT enzyme in LN patients. such a biochemical deficit is likely to originate from the adrenal medulla, which is the primary site of EPI synthesis. The adrenal medulla may be directly a ffected by the absence of hypoxanthine guanine phosphoribosyl transferase ( HPRT) enzyme, or may receive inappropriately high descending activation inp ut from the brain. The abnormally low DHPG levels, in the context of normal NE levels, indicates low MAO activity, either as a primary deficit, or as secondary adaptive changes to spare NE levels that would otherwise be too l ow for adequate noradrenergic function. [Neuropsychopharmacology 22:320-326 , 2000] Published by Elsevier Science Inc.